FRCPath Part 2—Revision Notes on Aspergillus spp.

(Oxford Textbook of Medical Mycology, Ch 10)

1. Genus at a glance

> 200 species; > 30 human pathogens—among the most ubiquitous environmental moulds; conidia inhaled daily. Characteristic aspergillum (asexual conidial head); despite known teleomorphs, the 2012 “one-fungus-one-name” rule retains Aspergillus nomenclature .Commercial uses: A. niger → citric-acid & enzyme production; A. oryzae → sake/soy fermentation .

2. Aspergillus Key species, temperatures, toxins & clinical points

Species (complex)

Opt. Temp / Range (°C)

Colony / Microscopy

Major toxin

Salient clinical facts

A. fumigatus

37 / 12-65

Green-blue; columnar uniseriate heads

Commonest invasive isolate; ABPA, CPA

A. flavus

37 / 12-48

Green-yellow; radiate uni/bi-seriate

Aflatoxin

Sinusitis, keratitis, aflatoxicosis risk

A. niger

37

Black biseriate heads

Otomycosis, onychomycosis

A. terreus

25-40

Beige; biseriate + accessory conidia

Ochratoxin

Intrinsic AmB-R

A. nidulans

37 / 2-48

Green with red-brown cleistothecia

CGD infections; AmB-R

A. versicolor

22-26 (opt); ≤40

White→yellow/green; penicillium-like

Sterigmatocystin

Onychomycosis; grows best at room-temp

A. clavatus

37

Long club-shaped vesicle

Extrinsic allergic alveolitis (“malt-worker’s lung”)

EORTC definitions

Proven:

Histologically proven and evidence of tissue damageGrowth of aspergillus from a sterile site

Probable

Host factor: neutropenia, transplant, cirrhosis, HIV, chronic lung disease, steroids, infleunza pneumonitisPresence in the lower respiratory tract: cytology, microscopy or growth OR GM >0.8 in BALF, >0.5 in serumRadiological factors: nodule, air crescent, cavity, wedge/segmental/lobar consolidation, tracehobrachial eschar or ulcer.

Green-yellow radiate, compare to A. fumigatus

Cinnamon colored, columnar

3. Epidemiology & reservoirs

Conidia in soil, rotting vegetation, damp building materials (wallpaper, concrete, pipe-lagging, carpets, HVAC); hospital construction dust → outbreaks .High-risk hosts: prolonged neutropenia, allogeneic-HSCT (~12 %), heart-lung Tx (11 %), CGD, high-dose steroids .CPA rising after TB, COPD, sarcoidosis .

4. Pathogenesis (4-step mnemonic I-G-A-T)

1 Inhalation & alveolar deposition

2 Germination when innate immunity fails

3 Angio-invasion → thrombosis, infarction

4 Toxins & hypersensitivity drive allergic / chronic disease

5. Clinical spectrum

Category

Typical entities / notes

Non-invasive

Otomycosis (A. niger), onychomycosis (A. versicolor), allergic fungal rhinosinusitis

Allergic

ABPA (≈16 % asthmatics); EAA by A. clavatus; SAFS

Chronic

CPA continuum: simple aspergilloma → chronic cavitary → fibrosing disease

Invasive

Acute pulmonary IA ± CNS, eye, skin; sinusitis; mortality 50–85 %

6. Diagnosis workflow

Direct / culture: septate 45° branching hyphae; Sabouraud agar 48-90 h. Serology & biomarkers:Aspergillus precipitins (IgG)—best single test for CPA/ABPA support .Galactomannan ELISA / LFD (false-pos with β-lactams) .(1→3) β-D-glucan (pan-fungal) .PCR on blood/BAL; combine with GM for ↑ sensitivity .Imaging: HR-CT halo sign → air-crescent; MRI for CNS/sinus. Histology/BAL/biopsy for EORTC “proven” disease.

7. Antifungal susceptibility & resistance

Azole-R A. fumigatus increasing in Europe (environmental TR34/L98H, TR46/Y121F/T289A). Intrinsic AmB-R: A. terreus, A. nidulans. Always request MICs on invasive isolates.

8. Management cheat-sheet

Condition

First-line

Key alternatives / notes

Invasive aspergillosis

Voriconazole

Liposomal AmB; isavuconazole (non-inferior; shortens QT c)

ABPA

Oral steroids ± itraconazole/posaconazole

CPA

Long-term oral triazole; monitor levels

Onychomycosis / Otomycosis

Topical clotrimazole ± oral azole

Surgical

Resection of solitary aspergilloma; debridement of sinus/CNS masses

Supportive: remove colonised lines, taper immunosuppression, give G-CSF if neutropenic.

9. Prognosis & prevention

IA mortality: 50-60 % (SOT) → 70-85 % (other immunosuppressed). Early targeted therapy improves survival .Primary prophylaxis (e.g. posaconazole in AML/allo-HSCT) cuts incidence but monitor for resistance.Environmental control: HEPA filtration, positive-pressure rooms, meticulous dust containment during building/refurbishment .

10. High-yield exam pearls

Columnar uniseriate head + growth to 65 °C = A. fumigatus. Accessory conidia → think A. terreus (and AmB-R). Galactomannan false-positive with piperacillin-tazobactam or Penicillium. Sterigmatocystin ↔ A. versicolor; ochratoxin ↔ A. terreus; aflatoxin ↔ A. flavus. Report isolates as “A. fumigatus complex” unless molecular ID performed (≥ 40 cryptic species) .Isavuconazole shortens QTc (contrast other azoles). Memorise EORTC/MSG 2008 possible/probable/proven definitions—frequent SAQ.Environmental reservoirs (damp concrete, carpets, HVAC) explain hospital outbreak questions. Room-temperature growth (~25 °C) onychomycosis isolate? Think A. versicolor.